Asthma has long been known to run in families. More recently, linkage studies have been conducted to identify specific genes involved. However, this work has gone slowly with multiple regions of linkage being identified. It is clear that gene-environment interactions are important in determining who develops asthma. Linkage studies conducted to date have not been designed to properly explore interactions. Given the complex nature of asthma, it is clear that candidate gene association studies will be necessary to identify disease genes and interactions with environmental factors. The role of air pollution in asthma exacerbation has long been appreciated. Ozone, an oxidant air pollutant, is one of the agents that can worsen existing asthma. Recent data suggest that ozone and other air pollutants may play a role in asthma etiology, but there are few data. Recent linkage studies in animals are beginning to identify genes that are involved in specific physiologic responses to ozone and other inhaled pollutants. This project includes several studies the role of genetic polymorphisms, environmental factors and their interaction in the etiology of childhood respiratory disease. The primary project is a family study of genetic susceptibility to asthma in a highly ozone exposed population, Mexico City. This study uses the case-parent triad design. We completed enrollment during FY2005 and are beginning genetic analyses based on the full dataset. In FY2005, we completed work on the cross-sectional examination of risk factors for respiratory disease among middle school students in Wuhan, China. We have published on the role of environmental tobacco smoke and coal burning in respiratory health during FY2005. We recently completed enrollment for a study examining whether a a commercially available cleaning device can be use for obtaining air samples for fungi as well as other airborne agents. We are analyzing the fungal data and will have the samples analyzed for endotoxin. We received funding from two other agencies to have a workshop in FY2006 to examine whether supplementation with omega-3 fatty acids during pregnancy might decrease the risk of asthma and atopy in the offspring. To examine this question in observational data, we have developed a collaboration with the ALSPAC study birth cohort. We have also begun a project using the Norway birth cohort, partially supported by NIEHS, to examine the question of whether serial pregnancies decrease the atopic status of the mother. This finding would be relevant to the hygiene hypothesis of asthma etiology.